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Keywords:

  • brain neoplasms;
  • central nervous system neoplasms;
  • epidemiology;
  • treatment effects;
  • surgery;
  • radiation;
  • chemotherapy;
  • late effects;
  • survivorship;
  • children;
  • adolescents;
  • young adults;
  • hypothyroidism;
  • growth deficiency;
  • stroke

Abstract

BACKGROUND

Survivors of childhood brain tumors (CBTs) are at high risk for a variety of late adverse effects. Most research on long-term effects of CBTs has been comprised of single-institution case series without comparison groups. Research on CBT late effects often is focused on neurologic and sensory outcomes, with less emphasis on other potential targets such as the endocrine and circulatory systems. The current study was conducted to contrast the incidence of endocrine and cardiovascular conditions among CBT survivors as a function of treatment and to determine the risk of occurrence of these conditions relative to a sibling comparison group.

METHODS

As part of the Childhood Cancer Survivor Study (CCSS), treatment data were collected from medical records and self-reported late effects were ascertained from a survey questionnaire of 1607 CBT patients who survived their disease for 5 or more years. For comparison purposes, questionnaire data were also collected from 3418 randomly selected siblings of participants in CCSS.

RESULTS

One or more endocrine conditions were reported by 43% of CBT survivors. Compared with siblings, CBT survivors had a significantly increased risk of late-onset (≥ 5 years postdiagnosis) hypothyroidism (relative risk [RR] = 14.3; 95% confidence interval [95% CI] 9.7–21.0), growth hormone deficiency (RR = 277.8; 95% CI 111.1–694.9), the need for medications to induce puberty (RR = 86.1; 95% CI 31.1–238.2), and osteoporosis (RR = 24.7; 95% CI 9.9–61.4). One or more cardiovascular conditions were reported by 18% of CBT survivors, with an elevated late-onset risk for stroke (RR = 42.8; 95% CI 16.7–109.8), blood clots (RR = 5.7; 95% CI 3.2–10.0), and angina-like symptoms (RR = 2.0; 95% CI 1.5–2.7). Very few late effects were evident among those treated with surgery only, but risks were consistently elevated for those treated with radiation and surgery, and higher still for those who also received adjuvant chemotherapy.

CONCLUSIONS

Childhood brain tumor survivors are at a significantly increased risk for several adverse endocrine and cardiovascular late effects, particularly if they were treated with radiation and chemotherapy. Lifetime medical surveillance and follow-up for potential toxicities are necessary because treatment-related complications may occur many years after therapy. Cancer 2003;97:663–73. © 2003 American Cancer Society.

DOI 10.1002/cncr.11095